This study involves the use of explants from neonatal rat brain maintained in long-term tissue culture as a model for in situ development 28-31,34. These explants show organotypic development in time periods comparable to those observed in situ. Glycolytic and citric acid cycle enzyme activities also show comparable developmental patterns in culture 31. The first part of this study will extend these observations to the development of respiration in explants and of oxidative phosphorylation in mitochondria isolated from the maturing explants. In the second part of this proposal, the explanted tissue will be used to study the capacity for and sequelae of seizure activity in the immature brain. Seizures in human infants probably result in hypoxic changes with high neurologic morbidity 4-7,9. In the first 40 days of post-natal life, the rat brain is developmentally comparable to the human brain from 6 months gestation to 18 months post-natal 14. The rat brain, in situ and in culture, can effect sustained seizure activity by age 7 days 27, when the pathways for carbohydrate energy metabolism are not mature. The hypothesis that neurologic damage occurs as a result of this imbalance of energy demand and supply in the seizing immature brain will be tested by exposing explants of varying ages to high potassium solutions with excess or minimal amounts of glucose as substrate. Changes in electrical activity and O2 consumption will be monitored. At 1 month of age, these explants will be studied for changes, compared to control explants in respiratory capacity, mitochondrial function, electrical activity, and in morphology.